The objective of this study is to investigate the effects of drugs which are abused on the enzymes regulating the synthesis of biogenic amines. The initial emphasis has been to determine the effects of amphetamines on tyrosine hydroxylase (TH) activity in the corpus striatum and substantia nigra. Large doses of methamphetamine depressed TH activity in the corpus striatum and substantia nigra. Evidence has been accumulated to indicate that this depression of enzyme activity occurs through a release of dopamine by methamphetamine from the nerve terminals of the nigro-striatal pathway located in the corpus striatum. This results in an intense stimulation of postsynaptic receptors which appears to activate a striato-nigral neuronal pathway producing a feedback inhibition of the substantia nigra. TH activity after methamphetamine was depressed, first in the substantia nigra and subsequently in the corpus striatum, which is compatible with a hypothesized inhibitory pathway from the corpus striatum to the substantia nigra. Studies are continuing in an effort to substantiate further this mechanism as well as to determine the effects of other drugs which are currently abused on the enzymes involved in biogenic amine synthesis.